1. Enhancing the Immune Surveillance in Multiple Myeloma Via CDK4/6 Inhibition
- Author
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Xu, Yan, Yao, Yao, Park, Woojun Daniel, Derebail, Sanika, Chakraborty, Chandraditya, Mu, Shidai, Alonso Fernández, Rafael, Talluri, Srikanth, Chyra, Zuzana, Wen, Kenneth, Yan, Qingsheng, Idahor, Osasenaga, Cipri, Selene, Prabhala, Rao, Anderson, Kenneth, Samur, Mehmet K., Fulciniti, Mariateresa, and Munshi, Nikhil C.
- Abstract
Deregulation of cyclin D genes is a uniform event in multiple myeloma (MM) and represent a striking addiction as observed in pan-cancer genome-wide CRISPR screening data. However, early stage Cyclin D and other cell cycle kinases inhibitors have shown a lack of single agent activity suggesting that targeting of cell cycle regulation is insufficient to produce a durable response in MM. Recent evidence recognizes the Cyclin D and CDK4 activities within the immune tumor microenvironment, supporting a previously unrecognized immunomodulatory functions of CDK4/6. This is particularly important in MM, a highly heterogeneous disease that resides in a complex ecosystem comprising of immune, endothelial, and stromal cells. We here evaluated the tumor intrinsic and extrinsic effects of CDK4/6 inhibition in MM with the goal to define rationally designed combination strategies to effectively impact MM growth.
- Published
- 2020
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